Antiviral protein

Antiviral proteins are proteins that are induced by human or animal cells to interfere with viral replication. These proteins are isolated to inhibit the virus from replicating in a host's cells and stop it from spreading to other cells.[1] The Pokeweed antiviral protein and the Zinc-Finger antiviral protein are two major antiviral proteins that have undergone several tests for viruses, including HIV and influenza.[2][3]

Pokeweed Antiviral Protein

The pokeweed plant is a common plant that is often used as a dye; it is also eaten when the plant is young and tender. Studies and experiments have shown that a specific protein, the Pokeweed Antiviral Protein (PAP), could possibly be used as a thereputical use in T-cell leukemia, lymphoma, Hodgkin's lymphoma, and AIDS. In an experiment posted in the Journal of Virology, mice immune systems were integrated to mimic that of humans. The mice were then infected with HIV and later given the PAP. The experiment showed that the PAP cured the mice from the HIV and with no side-effects. Due to these experiments, the U.S. Food and Drug Administration approved of using PAP on HIV patients in the U.S., and the Medicines Control Council of South Africa approved the use for African HIV patients. Research is still being conducted with PAP to see the effectiveness on other viruses including the common cold.[4]

Zinc-Finger Antiviral Protein

The Zinc-Finger Antiviral Protein (ZAP) is a specific antiviral protein that aids in the destruction of virus particles, specifically the Moloney murine leukemia virus (MLV) and the Sindbis virus (SIN). ZAP prevents the viral mRNA from building up inside the cell.[5] ZAP is specifically coded for certain target mRNA. Once a correct viral mRNA is detected, it recruits an RNA exosome complex to break down and destroy the viral RNA.[6] S. Miller and colleagues at the Bernhard Nocht Institute for Tropical Medicine stated that:

Antiviral effects were observed after infection of cells expressing the N-terminal part of ZAP fused to the product of the zeocin resistance gene (NZAP-Zeo) as well as after infection of cells inducibly expressing full-length ZAP. EBOV was inhibited by up to 4 log units, whereas MARV was inhibited between 1 to 2 log units. The activity of ZAP was dependent on the integrity of the second and fourth zinc finger motif, as tested with cell lines expressing NZAP-Zeo mutants. Heterologous expression of EBOV-and MARV-specific sequences fused to a reporter gene suggest that ZAP specifically targets L gene sequences. The activity of NZAP-Zeo in this assay was also dependent on the integrity of the second and fourth zinc finger motif. Time-course experiments with infectious EBOV showed that ZAP reduces the level of L mRNA before the level of genomic or anti genomic RNA is affected. Transient expression of ZAP decreased the activity of an EBOV replicon system by up to 95%. This inhibitory effect could be partially compensated for by overexpression of L protein.
— [7]

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Fighting Influenza

Researchers at Harvard Medical School (HMS) have found an antiviral protein, IFITM3 that could slow and even prevent deadly viruses from infecting and spreading. These proteins account for up to half of the immune system in humans and the other half is composed of interferons. In a few experiments, this certain antiviral protein defended cells from viruses such as influenza (including influenza A virus subtype H1N1), West Nile virus, dengue virus, and HIV-1.[8] The protein family, interferon-inducible transmembrane proteins (IFITM), were discovered about 25 years ago and are activated by an interferon. Not much is known about this protein, but it is found in many creatures and has been around for possibly millions of years.[9] "The most distinctive property of the first-line IFITM3 defense is its preventive action before the virus can fuse with the cell,"[10] said virologist Michael Farzan, associate professor of microbiology and molecular genetics at HMS and the New England Primate Research Center. A person's susceptibility to viral infections could be linked to variations in this antiviral protein and also how severe a person reacts to certain viruses like influenza or the more dangerous H1N1 strain.[11]

Recently, further work from the Wellcome Trust Sanger Institute has demonstrated for the first time that organisms with no IFITM3 display increased susceptibility to an influenza A infection; showing more severe symptoms than normal. This work was expanded by showing that a human variant of IFITM3 exists, with around 1/400 people carrying a mutated form of the gene, that may increase their risk of contracting severe influenza virus infection.[12]

References

  1. ↑ Houghton Mifflin Company. American Heritage Stedman's Medical Dictionary. (n.d.). Retrieved from http://dictionary.reference.com/browse/antiviral+protein?&qsrc=.
  2. ↑ The McGraw-Hill Companies. Pokeweed Antiviral Protein. (n.d.). Retrieved from http://www.mhhe.com/biosci/pae/botany/botany_map/articles/article_46.html.
  3. ↑ "Harvard Medical School; Scientists discover natural flu-fighting protein in human cells." Drug Week 2010. 1007. Web. 10 Sep 2010. Galileo. Lexis Nexis Academic. Retrieved at Georgia Southern University Henderson Library. <http://www.lexisnexis.com/hottopics/lnacademic/>.
  4. ↑ The McGraw-Hill Companies. Pokeweed Antiviral Protein. (n.d.). Retrieved from http://www.mhhe.com/biosci/pae/botany/botany_map/articles/article_46.html.
  5. ↑ "Antivirals; Researchers' work from Chinese Academy of Sciences focuses on antivirals." Drug Week 2007. 64. Web. 10 Sep 2010. Galileo. Lexis Nexis Academic. Retrieved at Georgia Southern University Henderson Library. <http://www.lexisnexis.com/hottopics/lnacademic/>.
  6. ↑ "Enzyme Research; New findings from G.F. Chen and co-researchers in the area of enzyme research described." Biotech Business Week 2008. Web. 10 September 2010.
  7. ↑ "Virology; Bernhard Nocht Institute for Tropical Medicine, Department of Virology reports research in virology." Drug Week 2007. 342. Web. 10 Sep 2010. Galileo. Lexis Nexis Academic. Retrieved at Georgia Southern University Henderson Library. <http://www.lexisnexis.com/hottopics/lnacademic/>.
  8. ↑ Lu J, Pan Q, Rong L, Liu S-L, Liang C (2010) The IFITM proteins inihibit HIV-1 infection. J Virol 85: 2126–2137.<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3067758/>
  9. ↑ "Harvard Medical School; Scientists discover natural flu-fighting protein in human cells." Drug Week 2010. 1007. Web. 10 Sep 2010. Galileo. Lexis Nexis Academic. Retrieved at Georgia Southern University Henderson Library. <http://www.lexisnexis.com/hottopics/lnacademic/>.
  10. ↑ "Harvard Medical School; Scientists discover natural flu-fighting protein in human cells." Drug Week 2010. 1007. Web. 10 Sep 2010. Galileo. Lexis Nexis Academic. Retrieved at Georgia Southern University Henderson Library. <http://www.lexisnexis.com/hottopics/lnacademic/>.
  11. ↑ "Harvard Medical School; Scientists discover natural flu-fighting protein in human cells." Drug Week 2010. 1007. Web. 10 Sep 2010. Galileo. Lexis Nexis Academic. Retrieved at Georgia Southern University Henderson Library. <http://www.lexisnexis.com/hottopics/lnacademic/>.
  12. ↑ http://www.bbc.co.uk/news/health-17474197
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